# A pharmaco-imaging approach to predicting social functioning and clinical responses to oxytocin administration in schizophrenia

> **NIH VA I01** · VETERANS AFFAIRS MED CTR SAN FRANCISCO · 2020 · —

## Abstract

Schizophrenia is a devastating illness that is characterized by deficits in social functioning. Social ability
deficits, such as poor verbal and nonverbal social skills, negative symptoms, such as decreased motivation
and emotional expressivity, and impaired theory of mind (ToM), the ability to understand the mental states of
others, contribute to poor social functioning and are unresponsive to antipsychotic medications. Oxytocin (OT),
a neuropeptide known to play a key role in social behavior, has shown promise as a potential treatment for
these deficits. However, trials conducted thus far have yielded mixed findings, stalling translation of research
into clinical practice. This is likely because these trials 1) have been underpowered and limited by use of a
single dosage of OT, 2) have sub-optimally assessed negative symptoms, 3) have not focused on clinically
relevant deficits such as social functioning and ToM outside of positive and negative symptoms, 4) have lacked
standardized drug administration and adherence monitoring protocols, and 5) have failed to account for
variability in factors that moderate OT effects at the individual level. Furthermore, we do not understand the
neural mechanisms of OT effects, which impairs our ability to predict who will respond to OT. The proposed
study will address each of these limitations to rigorously determine the ability of OT to improve real-world social
functioning in patients with schizophrenia. Adequate power, including two dosages of OT, state of the art
outcome measures, remote administration and adherence monitoring, and moderator analyses will address
methodological shortcomings in the extant literature. In addition, the proposed study will provide critical
information regarding the neural mechanisms of OT effects. Preliminary results show that a single intranasal
dose of OT improves ToM and negative symptoms in patients with schizophrenia. Furthermore, hypo-activation
in the right temporo-parietal junction (rTPJ) during ToM correlates with negative symptom severity in patients
with schizophrenia. Acute OT administration increases both rTPJ activation and behavioral performance during
ToM tasks and these increases are correlated. Thus, OT-induced rTPJ activation increases during ToM tasks
may be the mechanism of OT's effects on social functioning. The proposed study aims are to: 1) compare the
acute effects of a single administration of two dosages of OT, relative to placebo, on fMRI rTPJ activity and
behavioral accuracy during ToM task performance in SZ, 2) compare the clinical and behavioral effects of two
dosages of chronic OT treatment, relative to placebo, in SZ patients, and 3) determine if acute fMRI rTPJ
responses to a single OT administration predicts clinical responses to chronic OT treatment in SZ patients.
One hundred and fifty veterans will be randomized to receive either 20IU or 40IU of OT in a placebo-controlled,
within-subject, pharmaco-fMRI study in which their neural responses...

## Key facts

- **NIH application ID:** 9774675
- **Project number:** 1I01CX001761-01A2
- **Recipient organization:** VETERANS AFFAIRS MED CTR SAN FRANCISCO
- **Principal Investigator:** Josh Woolley
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2019-10-01 → 2024-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9774675

## Citation

> US National Institutes of Health, RePORTER application 9774675, A pharmaco-imaging approach to predicting social functioning and clinical responses to oxytocin administration in schizophrenia (1I01CX001761-01A2). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9774675. Licensed CC0.

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